This Program Project proposal is focused on obtaining the deepest understanding possible of the folding of a single RNA, the Tetrahymena group I ribozyme. For this reason, a central Core responsible for the creation of common RNA reagents, the basic training of personnel, and the documentation and distribution of materials. The Molecular Biology, Chemistry and Biochemistry (MBCB) Project Core will consist of a molecular biology and chemistry laboratory with a technical staff skilled in the preparation of RNA and mutagenesis. The core is essential for the production of the large quantities of RNA required for some of the proposed biophysical experiments. The central production of RNA will also insure its consistency for all of the Component Projects. The core will also perform routine folding, stability and activity assays to provide basic characterizations of new constructs and to demonstrate that all products meet a level of quality and purity commensurate with demands of all the Component Projects.